Abstract:

This thesis describes evaluation of a gastric retention device (GRD)
developed at Oregon State University. The device was originally fabricated from
Xanthan gum and Locust bean gum. A modified gastric retention device
containing other additives was developed and investigated in this work. The
modified device was evaluated in vitro for swelling and dissolution properties using
riboflavin as a model drug. Different shapes and sizes of GRDs were tested in dogs
to study the gastric retention potential of these devices. The effect of the device on
food emptying from the stomach in dogs was also investigated. Endoscopic studies
in dogs also showed that the device swells rapidly and considerably in gastric fluid.
The bioavailability of riboflavin from three different size GRDs was
determined in six fasted human volunteers and compared to an immediate release
formulation. The biostudy indicated that the bioavailability of riboflavin from a
large size GRD was more than triple that measured after administration of the
immediate release formulation. Deconvolution was used to determine gastric
residence time of the different size GRDs.
A new colonic delivery system made of acetaminophen loaded beads
produced by extrusion and spheronization and coated with different ratios of pectin
and ethylcellulose coating solutions in a spray coating apparatus was also
developed in this work. Such beads release their drug content in the colon due to
susceptibility of pectin in the outer coat to enzymatic action of colonic bacteria.
The new delivery system was evaluated in vitro by conducting release studies in
different dissolution media to mimic transit times, pH and enzyme conditions in the
gastrointestinal tract. The gastrointestinal transit behavior of drug beads was also
assessed by conducting gamma-scintigraphic studies in dogs.
The bioavailability and pharmacokinetic parameters of acetaminophen from
several colonic delivery system formulations were determined in human volunteers
and compared to the immediate release commercial product Tylenol®. A selected
pectin-ethylcellulose coat formulation in the ratio 1:3 was further evaluated in six
volunteers under both fed and fasting conditions and was found to be effective and
to provide sustained drug release in the colon over a period of 12 hours.